Fig 1.
Genomic landscape of the class 1 integron reported in the present study.
From left to right, the components are as follows: the direct repeat (DR1) formed by the insertion of Tn6005; the inverted repeat for Tn6005 (IRp); Tn21-like transposition genes tnpA and tnpR; the direct repeat (DR2) formed by the insertion of Tn6006; the inverted repeat for Tn6006/6007 (IRi); a class 1 integron with intI1 and integron-associated recombination site attI1, carrying two gene cassettes, MN039 and qacE2, each with a cassette-associated recombination site attC; Tn402-like transposition genes tniR, tniQ, tniB, tniA; the inverted repeat for Tn6007 (IRt); genes MN040 and MN041; the inverted repeat for Tn6008 (IRi); the Tn6008 transposon, carrying genes MN042, ahpD, MN043, MN044, MN045, MN046, and tniA; the inverted repeat for Tn6006/6008 (IRt); the direct repeat (DR2) formed by the insertion of Tn6006; Tn21-like mer operon consisting of urf-2Y, merE, merD, merA, merC, merP, merT and merR; the inverted repeat for Tn6005 (IRm); and the direct repeat (DR1) formed by the insertion of Tn6005. This whole element is embedded in an IncP plasmid whose sequence is lodged as accession number KY126370.
Fig 2.
Detailed structure of the class 1 integron promoter regions.
The -35 and -10 motifs for the Pc and PintI1 promoters are boxed; a point mutation in the -10 motif, which distinguishes the PcW and PcH1 promoters, is highlighted in red; the transcription initiation sites are indicated by arrows; the LexA box is shaded in blue (expression of intI1 is regulated by the SOS response). (A) Promoter region within the class 1 integron described in the present study, containing the PcW promoter variant, which is also present in a number of chromosomal class 1 integrons (accession numbers EU316185 and EU327987-EU327991). This strongly suggests PcW is the ancestral promoter in these integrons; (B) Promoter region within the otherwise identical class 1 integron characterized from the human fecal flora by Labbate et al. (23), which contains the PcH1 promoter.
Fig 3.
A model for the origin of clinical class 1 integrons.
(A) Diverse chromosomal class 1 integrons that are present in environmental Betaproteobacteria can interact with mobile DNA elements such as transposons and plasmids in the environment. Integrons have access to a vast pool of integron gene cassettes including the qacE cassette that encodes a membrane efflux pump; (B) A single chromosomal integron is captured by a Tn5090-like transposon, to generate Tn402; (C) Now mobilized, the integron is free to move between a range of bacterial species. In particular, the Tn402 transposon inserts into the mercury resistance Tn501-like transposon, to generate Tn21. Residence of this complex DNA element on a broad host range plasmid allows the integron to make its way into the human commensal flora via food-borne bacteria; (D) Once resident within the human microbiota, the integron is fixed by selection, driven by mercury and disinfectants, and after introduction of sulfonamide antibiotics, captures the sul1 and orf5 gene cassettes to delete part of the original qacE cassette; (E) Partial deletions of the tni module, and the collective acquisition of diverse resistance cassettes, lead to the diversity of clinical class 1 integrons that have since disseminated around the globe.